Influence of dosage schedule on the biological characteristics of N-nitrosomethylurea-induced rat mammary tumors.
Influence of dosage schedule on the biological characteristics of N-nitrosomethylurea-induced rat mammary tumors.
复制标题
剂量方案对N-亚硝基甲基脲诱导的大鼠乳腺肿瘤生物学特性的影响。
作者：
D. Rose;B. Pruitt;P. Stauber;E. Ertürk;G. Bryan
研究了用N -亚硝基甲脲两种诱导方式在雌性Sprague-Dawley大鼠中产生肿瘤的发生率、潜伏期和激素依赖性。在一组150只动物中，以5 mg/100 g体重的剂量间隔4周静脉注射三次致癌物（方法1）;第二组150只动物以相同剂量间隔1周两次注射（方法2）。肿瘤出现，具有相对较短的潜伏期，在98%的大鼠治疗的方法1，但在只有46%的治疗的方法2。所有的110个肿瘤产生的方法1进行组织学检查是癌，具有高度恶性的特征指示; 54.5%被归类为髓样癌。相比之下，56.5%的肿瘤诱导的方法2是分化良好的囊性乳头状腺癌，4个纤维腺瘤。方法1诱发的肿瘤对卵巢切除术的反应各不相同; 21例活检肿瘤中，10例（48%）完全缓解，7例（33%）部分缓解，但其中3例（14%）在6周内重新进展。同样，12例方法1诱导的癌中有8例（67%）对他莫昔芬有反应，5例（42%）在治疗6周后仍处于缓解状态。所有，但1的8卵巢切除大鼠的方法2引起的癌症进行了完全缓解，这是维持6周或更长时间;他莫昔芬产生完全缓解6和逮捕的7方法2引起的癌症的生长。雌激素受体的检测，但3%的96例癌方法1和91%的64例癌方法2诱导。受体水平和对内分泌操作的反应之间没有明确的关系。
The incidence, latent period, and hormone dependence of tumors produced in female Sprague-Dawley rats by two modes of induction with N -nitrosomethylurea were studied. In one group of 150 animals, the carcinogen was administered i.v. in three doses of 5 mg/100 g body weight given 4 weeks apart (Method 1); a second group of 150 animals received the same dose on two occasions 1 week apart (Method 2). Tumors appeared, with a relatively shorter latent period, in 98% of rats treated by Method 1 but in only 46% of those treated by Method 2. All of the 110 tumors produced by Method 1 examined histologically were carcinomas, with features indicative of a high degree of malignancy; 54.5% were classified as medullary carcinomas. In contrast, 56.5% of the tumors induced by Method 2 were well-differentiated cystic papillary adenocarcinomas; 4 were fibroadenomas. Carcinomas induced by Method 1 varied in their response to ovariectomy; of 21 biopsied tumors, 10 (48%) underwent a complete remission, and 7 (33%) underwent a partial remission, but progression was reestablished in 3 (14%) of these within 6 weeks. Similarly, 8 of 12 (67%) Method 1-induced carcinomas responded to tamoxifen, and 5 (42%) were still in remission after 6 weeks of treatment. All but 1 of 8 ovariectomized rats bearing carcinomas induced by Method 2 underwent a complete remission, which was maintained for 6 weeks or longer; tamoxifen produced complete remissions in 6 and arrested growth in 1 of 7 Method 2-induced carcinomas. Estrogen receptors were detected in all but 3% of 96 carcinomas induced by Method 1 and in 91% of 64 carcinomas induced by Method 2. No clear-cut relationship emerged between the receptor level and response to endocrine manipulation.